Molecular shape dynamics, reaction paths and conformational transitions in biomolecules. Theory and simulations.

我们的研究计划侧重于开发和应用理论和计算化学的工具来研究柔性分子中形状和动力学之间的相互作用。我们的方法融合了结构，形状，能量和构型转变的概念，在一个原始的方式：分子被视为拓扑实体，而不是孤立的构象在最佳几何形状。通过研究这些属性如何持续在外部扰动下，我们建立：（一）分子形状的稳定性，（二）的因素，控制发病的构型转变，（三）发生新的物种沿着反应路径，和（四）的动态形状相似性比较这些物种。 分子的形状根据尺度的不同而不同。对于大分子，我们使用链的几何形状和拓扑结构来监测受约束的聚合物和蛋白质离子的构型转变。在较小的系统中，我们专注于量子态和电子结构如何受到外部场或核几何形状的非绝热变化的影响。我们的长期目标是将这些领域整合到一个单一的协议中，以研究生物聚合物中局部电子特性和全局构象运动之间的相互作用。预计今后五年的工作将扩展我们的方法，并将其应用于分析选定的现象。以下主要主题将是我们的优先事项：（a）接枝和外部驱动的聚合物与不同的拓扑结构的构象转变。 (b)模拟飞行时间质谱条件下无水蛋白质离子的稳定性和展开。(c)外场和核几何对电子过程反应路径曲率的影响。主题（a）和（B）依赖于聚合物理论、计算机模拟和我们研究链缠结的技术的结合。主题（c）涉及与蛋白质天然状态相关的运动和局部场引起的非绝热效应。后一种分析需要计算随外场变化的相干量子态中的非绝热振幅。我将继续在这些领域培训HQP，并在2010/2011年休假期间与瑞典的同事进行合作研究。

Our research program focuses on developing and applying the tools of theoretical & computational chemistry to study the interplay between shape and dynamics in flexible molecules. Our approach blends the notions of structure, shape, energetics, and configurational transitions in an original manner: molecules are seen as topological entities, instead of isolated conformers at optimal geometries. By studying how these properties persist under external perturbations, we establish: (i) the stability of molecular shape, (ii) the factors that control the onset of configurational transitions, (iii) the occurrence of new species along reaction paths, and (iv) a measure of dynamic shape similarity for comparing these species. Molecular shape is conveyed differently depending on scale. For macromolecules, we use chain geometry and topology to monitor configurational transitions in constrained polymers and protein ions. In smaller systems, we focus on how quantum states and electronic structure are affected by external fields or non-adiabatic changes in nuclear geometry. Our long-term goal is to integrate these areas into a single protocol to study the interplay between local electronic properties and global conformational motions in biopolymers. The work projected for the next five years will extend our methods and apply them to the analysis of selected phenomena. The following main themes will be our priorities: (a) Configurational transitions in grafted and externally-driven polymers with distinct topologies. (b) The stability and unfolding of anhydrous protein ions in conditions that simulate time-of-flight mass spectrometry. (c) Effect of external fields and nuclear geometry on the curvature for reaction paths for electronic processes. The themes (a) and (b) rely on a combination of polymer theory, computer simulations, and our techniques to study chain entanglement. Theme (c) deals with non-adiabatic effects caused by the motions and local fields associated with a protein native state. This latter analysis requires the computation of diabatic amplitudes in coherent quantum states that vary with external fields. I will continue to train HQPs in these areas, and pursue collaborative research with colleagues in Sweden during my sabbatical in 2010/2011.